The role of vascular endothelial growth factor (VEGF) in major depressive disorder: an update meta-analysis

Major depressive disorder (MDD) is a prevalent mental health condition characterized by persistent feelings of profound sadness, emptiness, or hopelessness, as well as a marked loss of interest or pleasure in almost all activities. Evidence indicates that vascular endothelial growth factor (VEGF) is essential for neuronal survival, angiogenesis, and synaptic connectivity, and is also involved in stress resilience and antidepressant mechanisms, offering new perspectives on the pathophysiology of MDD. Although several studies have examined the relationship between peripheral VEGF levels and MDD, their findings remain inconsistent or inconclusive. Therefore, this updated meta-analysis was conducted to clarify the role of VEGF in the etiology of MDD.

This study aimed to conduct an updated meta-analysis to investigate the relationship between plasma VEGF levels in patients with MDD compared to healthy controls (HCs).

Four databases, PubMed, Embase, Cochrane, and Web of Science, were systematically searched for the meta-analysis from their inception until December 2024. A total of 14 case-control studies involving 2,919 participants (1,256 patients with MDD and 1,663 HCs) were included. The meta-analysis utilized both the ratio of means (RoM) and the standardized mean difference (SMD) methods to enhance interpretability and clinical relevance.

The meta-analysis confirmed that patients with MDD had significantly higher VEGF levels compared to HCs (RoM = 1.21, 95% CI: 1.06-1.38, p < 0.001; SMD = 0.45, 95% CI: 0.13-0.77, p < 0.001).

The findings suggest that elevated plasma VEGF levels are associated with MDD, as indicated by the updated meta-analysis. A potential biological link between VEGF and MDD exists, offering important insights into the underlying pathophysiological mechanisms.

Not applicable.